First-in-human use of a modular capsid virus-like vaccine platform: an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2
Authors: Merel J Smit, Adam F Sander, Maud B P A Ariaans, Cyrielle Fougeroux, Constanze Heinzel, Rolf Fendel, Meral Esen, Peter G Kremsner, Rob ter Heine, Heiman F Wertheim, Manja Idorn, Søren Riis Paludan, Alexander P Underwood, Alekxander Binderup, Santseharay Ramirez, Jens Bukh, Max Soegaard, Sayit M Erdogan, Tobias Gustavsson, Stine Clemmensen, Thor G Theander, Ali Salanti, Mette Hamborg, Willem A de Jongh, Matthew B B McCall, Morten A Nielsen, Benjamin G Mordmüller, Merel J Smit, Adam F Sander, Maud B P A Ariaans, Cyrielle Fougeroux, Constanze Heinzel, Rolf Fendel, Meral Esen, Peter G Kremsner, Rob ter Heine, Heiman F Wertheim, Manja Idorn, Søren Riis Paludan, Alexander P Underwood, Alekxander Binderup, Santseharay Ramirez, Jens Bukh, Max Soegaard, Sayit M Erdogan, Tobias Gustavsson, Stine Clemmensen, Thor G Theander, Ali Salanti, Mette Hamborg, Willem A de Jongh, Matthew B B McCall, Morten A Nielsen, Benjamin G Mordmüller, Robert Dagil, Louise Goksøyr, Thomas M Hulen, Christoph Janitzek, Daniel S Jensen, Sune Justesen, Paul K Khalifé, Andrea Kreidenweiss, Telma Lança, Olivia Lie-Andersen, Karina Teelen, Elena Vidal-Calvo
Journal: The Lancet Microbe (2023)

Capsid virus-like particles (cVLP) have proven safe and immunogenic and can be a versatile platform to counter pandemics. We aimed to clinically test a modular cVLP COVID-19 vaccine in individuals who were naive to SARS-CoV-2.In this phase 1, single-centre, dose-escalation, adjuvant-selection, open-label clinical trial, we recruited participants at the Radboud University Medical Center in Nijmegen, Netherlands, and sequentially assigned them to seven groups. Eligible participants were healthy, aged 18-55 years, and tested negative for SARS-CoV-2 and anti-SARS-CoV-2 antibodies. Participants were vaccinated intramuscularly on days 0 and 28 with 6 μg, 12 μg, 25 μg, 50 μg, or 70 μg of the cVLP-based COVID-19 vaccine (ABNCoV2). A subgroup received MF59-adjuvanted ABNCoV2. Follow-up was for 24 weeks after second vaccination. The primary objectives were to assess the safety and tolerability of ABNCoV2 and to identify a dose that optimises the tolerability-immunogenicity ratio 14 days after the first vaccination. The primary safety endpoint was the number of related grade 3 adverse events and serious adverse events in the intention-to-treat population. The primary immunogenicity endpoint was the concentration of ABNCoV2-specific antibodies. The trial is registered with ClinicalTrials.gov, NCT04839146.45 participants (six to nine per group) were enrolled between March 15 and July 15, 2021. Participants had a total of 249 at least possibly related solicited adverse events (185 grade 1, 63 grade 2, and one grade 3) within a week after vaccination. Two serious adverse events occurred; one was classified as a possible adverse reaction. Antibody titres were dose-dependent with levels plateauing at a vaccination dose of 25-70 μg ABNCoV2. After second vaccination, live virus neutralisation activity against major SARS-CoV-2 variants was high but was lower with an omicron (BA.1) variant. Vaccine-specific IFNγ+ CD4+ T cells were induced.Immunisation with ABNCoV2 was well tolerated, safe, and resulted in a functional immune response. The data support the need for additional clinical development of ABNCoV2 as a second-generation SARS-CoV-2 vaccine. The modular cVLP platform will accelerate vaccine development, beyond SARS-CoV-2.EU, Carlsberg Foundation, and the Novo Nordisk Foundation.